tbuckley/cabot-search huggingface dataset:
Platelet Detection Based on Improved YOLO_v3
Authors: Renting Liu, Chunhui Ren, Miaomiao Fu, Zhengkang Chu, Jiuchuan Guo
Journal: Cyborg and Bionic Systems (2022)

Platelet detection and counting play a greatly significant role in medical field, especially in routine blood tests which can be used to judge blood status and diagnose related diseases. Therefore, platelet detection is valuable for diagnosing related blood diseases such as liver-related diseases. Blood analyzers and visual microscope counting were widely used for platelet detection, but the experimental procedure took nearly 20 minutes and can only be performed by a professional doctor. In recent years, technological breakthroughs in artificial intelligence have made it possible to detect red blood cells through deep learning methods. However, due to the inaccessibility of platelet datasets and the small size of platelets, deep learning-based platelet detection studies are almost nonexistent. In this paper, we carried out experiments for platelet detection based on commonly used object detection models, such as Single Shot Multibox Detector (SSD), RetinaNet, Faster_rcnn, and You Only Look Once_v3 (YOLO_v3). Compared with the other three models, YOLO_v3 can detect platelets more effectively. And we proposed three ideas for improvement based on YOLO_v3. Our study demonstrated that YOLO_v3 can be adopted for platelet detection accurately and in real time. We also implemented YOLO_v3 with multiscale fusion, YOLO_v3 with anchor box clustering, and YOLO_v3 with match parameter on our self-created dataset and, respectively, achieved 1.8% higher average precision (AP), 2.38% higher AP, and 2.05% higher AP than YOLO_v3. The comprehensive experiments revealed that YOLO_v3 with the improved ideas performs better in platelet detection than YOLO_v3.
Evaluation of Periodic Breast Cancer Screening With Mammography
Authors: Sam Shapiro
Journal: JAMA (1966)

Periodic breast cancer screening with mammography and clinical examination is being evaluated to determine its value in reducing breast cancer mortality among women. Representative samples of women aged 40 to 64 years enrolled in the Health Insurance Plan of Greater New York are randomly assigned to study and control groups, each of which will contain 30,000 women. Results of the study to date are consistent with the hypothesis that the screening leads to earlier detection of breast cancers than is ordinarily experienced and that mammography contributes significantly to detection. While these relationships are encouraging, they must be viewed with caution since the study is still in its early stages. Furthermore, the crucial question is whether mortality from breast cancer is lowered because of the screening, and definitive findings on this issue will require at least five years of follow-up.
Myeloid expression of the anti-apoptotic protein Mcl1 is required in anti-myeloperoxidase vasculitis but myeloperoxidase inhibition is not protective
Authors: Fernanda Florez-Barros, Siobhan Bearder, Bengt Kull, Adrian Freeman, Attila Mócsai, Michael G. Robson
Journal: Kidney International (2022)

Antibodies to neutrophil and monocyte myeloperoxidase and proteinase 3 are a feature of anti-neutrophil cytoplasmic antibody vasculitis, a disease with significant morbidity for which new treatments are needed. Mice with a myeloid-specific deletion of the anti-apoptotic protein Mcl1 have reduced numbers of circulating neutrophils. Here, we assessed if myeloid-specific Mcl1 was required in murine anti-myeloperoxidase vasculitis and whether inhibition of myeloperoxidase was protective. In a murine model of anti-neutrophil cytoplasmic antibody vasculitis, induced by anti-myeloperoxidase antibody, mice with a myeloid-specific deletion of Mcl1 were protected from disease. They had fewer crescents, neutrophils, and macrophages in the glomeruli, lower serum creatinine levels and reduced albuminuria compared with controls. At baseline and day six after disease induction they had fewer circulating neutrophils than controls. At day six there were also fewer circulating monocytes. Myeloperoxidase inhibition with AZD5904 had no effect on histological or biochemical parameters of disease, and there was also no reduction in albuminuria at day one, two, five or seven after disease induction. These findings persisted when disease was induced without granulocyte-colony stimulating factor, which increases disease severity. A second myeloperoxidase inhibitor, AZM198, also showed no evidence of an effect, although both AZD5904 and AZM198 inhibited human neutrophil extracellular trap formation in vitro. Thus, our results show that while myeloid-specific Mcl1 is required in this model of anti-myeloperoxidase vasculitis, myeloperoxidase inhibition is not protective.
Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study
Authors: Thorir Einarsson Long, Olafur Skuli Indridason, Runolfur Palsson, Sæmundur Rognvaldsson, Thorvardur Jon Love, Sigrun Thorsteinsdottir, Ingigerdur Solveig Sverrisdottir, Brynjar Vidarsson, Pall Torfi Onundarson, Bjarni Agnar Agnarsson, Margret Sigurdardottir, Ingunn Thorsteinsdottir, Isleifur Olafsson, Asdis Rosa Thordardottir, Elias Eythorsson, Asbjorn Jonsson, Gauti Gislason, Andri Olafsson, Hlif Steingrimsdottir, Malin Hultcrantz, Brian G. M. Durie, Stephen Harding, Ola Landgren, Sigurdur Yngvi Kristinsson
Journal: Blood Cancer Journal (2022)

Abstract Serum free light chain (FLC) concentration is greatly affected by kidney function. Using a large prospective population-based cohort, we aimed to establish a reference interval for FLCs in persons with chronic kidney disease (CKD). A total of 75422 participants of the iStopMM study were screened with serum FLC, serum protein electrophoresis and immunofixation. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Central 99% reference intervals were determined, and 95% confidence intervals calculated. Included were 6461 (12%) participants with measured FLCs, eGFR &lt; 60 mL/min/1.73 m 2 , not receiving renal replacement therapy, and without evidence of monoclonality. Using current reference intervals, 60% and 21% had kappa and lambda FLC values outside the normal range. The FLC ratio was outside standard reference interval (0.26–1.65) in 9% of participants and outside current kidney reference interval (0.37–3.10) in 0.7%. New reference intervals for FLC and FLC ratio were established. New reference intervals for the FLC ratio were 0.46–2.62, 0.48–3.38, and 0.54–3.30 for eGFR 45–59, 30–44, and &lt; 30 mL/min/1.73 m 2 groups, respectively. The crude prevalence of LC-MGUS in CKD patients was 0.5%. We conclude that current reference intervals for FLC and FLC ratio are inaccurate in CKD patients and propose new eGFR based reference intervals to be implemented.
A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy
Authors: Ziyang Zhang, Peter J. Rohweder, Chayanid Ongpipattanakul, Koli Basu, Markus-Frederik Bohn, Eli J. Dugan, Veronica Steri, Byron Hann, Kevan M. Shokat, Charles S. Craik
Journal: Cancer Cell (2022)

Immunotargeting of tumor-specific antigens is a powerful therapeutic strategy. Immunotherapies directed at MHC-I complexes have expanded the scope of antigens and enabled the direct targeting of intracellular oncoproteins at the cell surface. We asked whether covalent drugs that alkylate mutated residues on oncoproteins could act as haptens to generate unique MHC-I-restricted neoantigens. Here, we report that KRAS G12C mutant cells treated with the covalent inhibitor ARS1620 present ARS1620-modified peptides in MHC-I complexes. Using ARS1620-specific antibodies identified by phage display, we show that these haptenated MHC-I complexes can serve as tumor-specific neoantigens and that a bispecific T cell engager construct based on a hapten-specific antibody elicits a cytotoxic T cell response against KRAS G12C cells, including those resistant to direct KRAS G12C inhibition. With multiple K-RAS G12C inhibitors in clinical use or undergoing clinical trials, our results present a strategy to enhance their efficacy and overcome the rapidly arising tumor resistance.
TBX20 Improves Contractility and Mitochondrial Function During Direct Human Cardiac Reprogramming
Authors: Yawen Tang, Sajesan Aryal, Xiaoxiao Geng, Xinyue Zhou, Vladimir G. Fast, Jianyi Zhang, Rui Lu, Yang Zhou
Journal: Circulation (2022)

Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as a promising strategy to remuscularize injured myocardium. However, it is insufficient to generate functional induced cardiomyocytes from human fibroblasts using conventional reprogramming cocktails, and the underlying molecular mechanisms are not well studied.To discover potential missing factors for human direct reprogramming, we performed transcriptomic comparison between human induced cardiomyocytes and functional cardiomyocytes.We identified TBX20 (T-box transcription factor 20) as the top cardiac gene that is unable to be activated by the MGT133 reprogramming cocktail (MEF2C, GATA4, TBX5, and miR-133). TBX20 is required for normal heart development and cardiac function in adult cardiomyocytes, yet its role in cardiac reprogramming remains undefined. We show that the addition of TBX20 to the MGT133 cocktail (MGT+TBX20) promotes cardiac reprogramming and activates genes associated with cardiac contractility, maturation, and ventricular heart. Human induced cardiomyocytes produced with MGT+TBX20 demonstrated more frequent beating, calcium oscillation, and higher energy metabolism as evidenced by increased mitochondria numbers and mitochondrial respiration. Mechanistically, comprehensive transcriptomic, chromatin occupancy, and epigenomic studies revealed that TBX20 colocalizes with MGT reprogramming factors at cardiac gene enhancers associated with heart contraction, promotes chromatin binding and co-occupancy of MGT factors at these loci, and synergizes with MGT for more robust activation of target gene transcription.TBX20 consolidates MGT cardiac reprogramming factors to activate cardiac enhancers to promote cardiac cell fate conversion. Human induced cardiomyocytes generated with TBX20 showed enhanced cardiac function in contractility and mitochondrial respiration.
Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential
Authors: Zhengjun Lin, Yanlin Wu, Yiting Xu, Guoqing Li, Zhihong Li, Tang Liu
Journal: Molecular Cancer (2022)

Abstract Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be obtained from various human tissues and organs. They can differentiate into a wide range of cell types, including osteoblasts, adipocytes and chondrocytes, thus exhibiting great potential in regenerative medicine. Numerous studies have indicated that MSCs play critical roles in cancer biology. The crosstalk between tumour cells and MSCs has been found to regulate many tumour behaviours, such as proliferation, metastasis and epithelial-mesenchymal transition (EMT). Multiple lines of evidence have demonstrated that MSCs can secrete exosomes that can modulate the tumour microenvironment and play important roles in tumour development. Notably, very recent works have shown that mesenchymal stem cell-derived exosomes (MSC-derived exosomes) are critically involved in cancer resistance to chemotherapy agents, targeted-therapy drugs, radiotherapy and immunotherapy. In this review, we systematically summarized the emerging roles and detailed molecular mechanisms of MSC-derived exosomes in mediating cancer therapy resistance, thus providing novel insights into the clinical applications of MSC-derived exosomes in cancer management.
Exploring the Long-term Outcomes of Active Surveillance Among Men With Prostate Cancer—Best for Whom?
Authors: Ahmed O. Elmehrath
Journal: JAMA Network Open (2022)

Eugenio Ventimiglia, MD; Anna Bill-Axelson, MD, PhD; Ola Bratt, MD, PhD; Francesco Montorsi, MD; Pär Stattin, MD, PhD; Hans Garmo, PhD
Innovation’s Disjointed Path From Approval to Payment—The Case of Embolic Protection Devices for Transcatheter Aortic Valve Replacement
Authors: Neel M. Butala, Andrew S. Oseran, Robert W. Yeh
Journal: JAMA Cardiology (2022)

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Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial
Authors: Sumanta Kumar Pal, Robert Uzzo, Jose Antonio Karam, Viraj A Master, Frede Donskov, Cristina Suarez, Laurence Albiges, Brian Rini, Yoshihiko Tomita, Ariel Galapo Kann, Giuseppe Procopio, Francesco Massari, Matthew Zibelman, Igor Antonyan, Mahrukh Huseni, Debasmita Basu, Bo Ci, William Leung, Omara Khan, Sarita Dubey, Axel Bex
Journal: The Lancet (2022)
Epidemiology of Renal Cell Carcinoma: 2022 Update
Authors: Laura Bukavina, Karim Bensalah, Freddie Bray, Maria Carlo, Ben Challacombe, Jose A. Karam, Wassim Kassouf, Thomas Mitchell, Rodolfo Montironi, Tim O'Brien, Valeria Panebianco, Ghislaine Scelo, Brian Shuch, Hein van Poppel, Christopher D. Blosser, Sarah P. Psutka
Journal: European Urology (2022)
Genetics and Pathogenesis of Parkinson's Syndrome
Authors: Hui Ye, Laurie A. Robak, Meigen Yu, Matthew Cykowski, Joshua M. Shulman
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

Parkinson's disease (PD) is clinically, pathologically, and genetically heterogeneous, resisting distillation to a single, cohesive disorder. Instead, each affected individual develops a virtually unique form of Parkinson's syndrome. Clinical manifestations consist of variable motor and nonmotor features, and myriad overlaps are recognized with other neurodegenerative conditions. Although most commonly characterized by alpha-synuclein protein pathology throughout the central and peripheral nervous systems, the distribution varies and other pathologies commonly modify PD or trigger similar manifestations. Nearly all PD is genetically influenced. More than 100 genes or genetic loci have been identified, and most cases likely arise from interactions among many common and rare genetic variants. Despite its complex architecture, insights from experimental genetic dissection coalesce to reveal unifying biological themes, including synaptic, lysosomal, mitochondrial, andimmune-mediated mechanisms of pathogenesis. This emerging understanding of Parkinson's syndrome, coupled with advances in biomarkers and targeted therapies, presages successful precision medicine strategies.
Recapture and retreatment rates with ixekizumab after withdrawal of therapy in patients with axial spondyloarthritis: results at week 104 from a randomised placebo-controlled withdrawal study
Authors: Robert B M Landewé, Denis Poddubnyy, Proton Rahman, Filip E Van den Bosch, Rebecca Bolce, Soyi Liu Leage, Jeffrey R Lisse, So Young Park, Lianne Gensler
Journal: Annals of the Rheumatic Diseases (2022)

<h3>Objectives</h3> To evaluate the recapture of response with open-label (OL) ixekizumab (IXE) retreatment at week 104 in patients with axial spondyloarthritis who flared after withdrawal of IXE therapy. <h3>Methods</h3> COAST-Y (NCT03129100) is a phase III extension study that included a double-blind, placebo-controlled, randomised withdrawal-retreatment period (RWRP). Patients who achieved remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) &lt;1.3 (inactive disease, ID) at least once at week 16 or 20 and &lt;2.1 (low disease activity, LDA) at both visits) were randomised 2:1 at week 24 to continue IXE or withdraw to placebo. Patients who subsequently flared were switched to OL IXE every 2 or 4 weeks (Q2W or Q4W) at the next visit. The proportions of patients who recaptured ASDAS LDA and ID were summarised for those who experienced flare. <h3>Results</h3> Of the 155 patients who entered the RWRP (placebo, n=53; IXE Q4W, n=48; IXE Q2W, n=54), 138 (89%) completed week 104. Of the placebo-treated patients (n=53), 28 (53%) experienced a flare during weeks 24–104; of these, 4 (14%) recaptured ASDAS LDA before retreatment with OL IXE, and 23 (82%) recaptured ASDAS LDA and 19 (68%) met ASDAS ID after retreatment. Of the continuously treated IXE patients (n=102), 13 experienced flare; 7 of 13 (54%) recaptured ASDAS LDA before switching to OL IXE retreatment, while 5 of 13 (38%) recaptured ASDAS LDA and 4 of 13 (31%) met ID after switching. <h3>Conclusions</h3> Ninety-six per cent of patients withdrawn to placebo recaptured at least ASDAS LDA and 71% recaptured ASDAS ID with IXE retreatment at week 104. This may provide support to patients who may require a brief interruption in therapy.
Gut microbiome associations with host genotype vary across ethnicities and potentially influence cardiometabolic traits
Authors: Ulrika Boulund, Diogo M. Bastos, Bart Ferwerda, Bert-Jan van den Born, Sara-Joan Pinto-Sietsma, Henrike Galenkamp, Evgeni Levin, Albert K. Groen, Aeilko H. Zwinderman, Max Nieuwdorp
Journal: Cell Host & Microbe (2022)
Letter to the editor: HuR in liver homeostasis
Authors: Grayson W. Way
Journal: Hepatology (2022)

To the editor, I read the recent paper by Subramanian et al.1 with great interest because the hepatocyte‐specific role of HuR in NAFLD/NASH pathophysiology is unclear. Understanding the underlying mechanisms by which HuR regulates hepatic lipid metabolism has the potential to advance the field of NAFLD/NASH research. Unfortunately, I do not believe that the conclusions made in the paper can be supported by the data for the reasons described below. In this paper, the authors stated that a hepatocyte‐specific HuR knockout mouse model was used. However, the model used in their experiments is liver‐specific, not hepatocyte‐specific, as albumin is expressed by both hepatocytes and cholangiocytes. This is an important distinction, as future studies using hepatocyte‐specific knockouts of HuR may yield different results, thus adding confusion to the scientific literature. The flow cytometry and cell identification methods used were not up to the field's standards. The gating strategy used calls the data into question. Cell populations were identified with markers that are not consistent with published standards for these cell types. The CD4− CD8− NK1.1+ cells are natural killer (NK) cells, not natural killer T (NKT) cells. NKT cells express CD3 and/or T‐cell receptor (TCR) along with NK1.1. In addition, their Supporting Methods sound like the same fluorophore, APC‐Cy7, was used for both CD8 and major histocompatibility complex II, which would make those markers indistinguishable. Their gating strategies for CD4 T cells and CD8 T cells were also questionable. They did not pregate on CD45, nor did they gate on any T cell–specific marker (i.e., CD90, TCR, or CD3). Identifying CD4 T cells and CD8 T cells based solely on the presence of CD4 and CD8 markers is not standard practice in the field. It is well‐known that both dendritic cells and NKT cells can express both CD4 and CD8.2,3 The flow cytometry cell preparations did not use anti‐CD16/32 (also known as Fc block) or other Fc blocking reagent (e.g., rat serum, nonspecific IgG) to prevent antibodies from binding via their Fc region to Fc gamma receptors rather than their intended targets through Fab‐antigen binding. Therefore, any cell expressing an Fc gamma receptor may stain positive for any or all of the antibodies used. Their flow cytometry data are highly irregular, which makes the conclusions questionable. In summary, our comments should not dissuade readers from the importance of this article, but it may be important to ask the authors to address these criticisms and/or submit an erratum.
Publisher Correction: Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease
Authors: Marta Milà-Alomà, Nicholas J. Ashton, Mahnaz Shekari, Gemma Salvadó, Paula Ortiz-Romero, Laia Montoliu-Gaya, Andrea L. Benedet, Thomas K. Karikari, Juan Lantero-Rodriguez, Eugeen Vanmechelen, Theresa A. Day, Armand González-Escalante, Gonzalo Sánchez-Benavides, Carolina Minguillon, Karine Fauria, José Luis Molinuevo, Jeffrey L. Dage, Henrik Zetterberg, Juan Domingo Gispert, Marc Suárez-Calvet, Kaj Blennow
Journal: Nature Medicine (2022)
Congenital Anomalies of the Kidney and Urinary Tract in Preterm Infants—Active Drivers of Increased Disease or Associated Bystanders?
Authors: Tahagod H. Mohamed, Jonathan L. Slaughter
Journal: JAMA Network Open (2022)

Thomas Hays, MD, PhD; Michaela V. Thompson, MD; David A. Bateman, MD; Rakesh Sahni, MD; Veeral N. Tolia, MD; Reese H. Clark, MD; Ali G. Gharavi, MD